We are currently analyzing the coexistence of calretinin (CR), a calcium binding protein, and tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of dopamine in the monkey substantia migra (SN) and ventral tegmental area (VTA). Thionin-stained sections have been used to create an atlas of the monkey SN region. On sections adjacent to the thionin stained material, we used double-labelling immunofluorescence to distinguish three distinct cell types; cells immunoreactive for CR only (CR+), cells immunoreactive for TH only (TH+) and cells in which both proteins were localized (CRTH). Unilateral injections of MPTP have been shown to produce a severe loss of TH cells in the substantia nigra on the injected side (down 70% in most cases), and is thought to provide an accurate animal model of Parkinson's disease. Preliminary results from one monkey treated with a unilateral injection of MPTP (4 mg/kg, right carotid artery) two and a half years prior to examination revealed a significant portion (20-30%) of cells in the unaffected substantia nigra compacta contained colocalized cells. In contrast, approximately 50-60% of the remaining VTA and SN cells on the lesioned side contained both proteins. The total number of TH only cells was significantly reduced, as expected. Two possibilities exist to explain this data: either those cells which remained after the lesion contained both proteins prior to the lesion or CR production was induced in a significant portion of the remaining TH immunoreactive cells. It thus appears that CR may protect numerous SN/VTA cells from destruction by MPTP.